Antithrombin heparan sulfate for detection and treatment of cancer

Abstract

Methods of detecting and treating an epithelial carcinoma, such as pancreatic ductal adenocarcinoma cancer or bladder cancer, expressing antithrombin-binding heparan sulfate (HSAT) in a subject, comprising combining a biological sample of the subject containing HSAT with antithrombin and detecting binding of HSAT and the antithrombin, optionally determining that the antithrombin inhibits factor Xa.

What is claimed is: 
     
         1 . A method of detecting antithrombin-binding heparan sulfate (HS AT ) in a biological sample comprising combining the biological sample with antithrombin and detecting binding of HS AT  and the antithrombin, thereby detecting HS AT  in the sample. 
     
     
         2 . The method of  claim 1 , wherein the HS AT  is detected by determining that the antithrombin/HS AT  complex inhibits factor Xa. 
     
     
         3 . The method of  claim 1 , wherein the HS AT  is detected by further detecting the antithrombin as a stain in immunohistochemistry, or as a tracer in in vivo imaging. 
     
     
         4 . The method of  claim 1 , wherein biological sample is a liquid biopsy, urine, blood or feces. 
     
     
         5 . The method of  claim 4 , wherein the biological sample is from a subject with pancreatic ductal adenocarcinoma (PDAC), bladder cancer or prostate cancer. 
     
     
         6 . A method of detecting a cancer expressing antithrombin-binding heparan sulfate (HS AT ) in a subject comprising combining a biological sample of the subject with antithrombin, and detecting binding of HS AT  and the antithrombin, thereby detecting the cancer in the subject. 
     
     
         7 . The method of  claim 6 , wherein the HS AT  is detected at a higher level than in a control subject. 
     
     
         8 . The method of  claim 6 , wherein the HS AT  is detected by determining that the antithrombin inhibits factor Xa. 
     
     
         9 . The method of  claim 6 , wherein biological sample is a biopsy, urine, blood or feces. 
     
     
         10 . The method of  claim 6 , wherein the HS AT  is detected by further detecting the antithrombin as a stain in immunohistochemistry, or as a tracer in in vivo imaging. 
     
     
         11 . The method of  claim 6 , wherein the cancer is pancreatic ductal adenocarcinoma (PDAC), bladder cancer or prostate cancer. 
     
     
         12 . A method of treating a cancer expressing antithrombin-binding heparan sulfate (HS AT ) in a subject comprising combining a biological sample of the subject containing HS AT  with antithrombin, detecting binding of HS AT  and the antithrombin, and treating the subject for the cancer by administering an effective amount of cancer therapy. 
     
     
         13 . The method of  claim 12 , wherein the HS AT  is detected at a higher level than in a control subject. 
     
     
         14 . The method of  claim 12 , wherein the HS AT  is detected by further determining that the antithrombin inhibits factor Xa. 
     
     
         15 . The method of  claim 12 , wherein biological sample is a biopsy, urine, blood or feces. 
     
     
         16 . The method of  claim 12 , wherein the HS AT  is detected by further detecting the antithrombin as a stain in immunohistochemistry, or as a tracer for in vivo imaging. 
     
     
         17 . The method of  claim 12 , wherein the cancer therapy comprises an effective amount of thrombin conjugated to a cancer therapy agent. 
     
     
         18 . A method of producing antithrombin-binding heparan sulfate (HS A T), comprising culturing mammalian bladder cancer cells and purifying HS AT  from the cultured cells. 
     
     
         19 . The method of  claim 18 , wherein the HS AT  is isolated from the surface of the cells. 
     
     
         20 . The method of  claim 18 , wherein the HS AT  is isolated from a secreted fraction of the cells.